The PI hypothesizes that a surface dehydrogenase (SDH) plays a critical role in the early events of infection by facilitating entry of group A streptococcus into pharyngeal cells. The author states that SDH is essential for survival of GAS and that SDH has multiple means of binding to several mammalian proteins and also has ADP-ribosylating activity. SDH interacts with mammalian pharyngeal cells and regulates the signal transduction pathways in pharyngeal cells which facilitates adherence and penetration of the host cell. Specific Aim 1. A 32 kDa pharyngeal cell membrane receptor for SDH will be purified and biochemically characterized Specific Aim 2. The receptor binding domain of SDH will be identified using several protein and site directed mutagenesis techniques to establish the molecular basis of SDH-pharyngeal cell receptor interaction. Specific Aim 3 Using intact streptococci and recombinant native and mutated SDH proteins, SDH mediated signaling pathways in pharyngeal cells will be elucidated by studying various intracellular signaling events. Specific Aim 4, native and mutated SDH will be covalently linked to fluorescinated microbeads to study adherence and invasion of cell lines.